1. Technical Field of the Invention
This invention relates to localized magnetic resonance spectroscopy (MRS) and to magnetic resonance spectroscopic imaging (MRSI) of the proton NMR signal, specifically to a magnetic resonance spectroscopy (MRS) method to measure a single volume of interest and to a magnetic resonance spectroscopic imaging method with at least one spectral dimension and up to three spatial dimensions. MRS and MRSI are sensitive to movement of the object to be imaged and to frequency drifts during the scan that may arise from scanner instability, field drift, respiration, and shim coil heating due to gradient switching. Inter-scan and intra-scan movement leads to line broadening and changes in spectral pattern secondary to changes in partial volume effects in localized MRS. In MRSI movement leads to ghosting artifacts across the entire spectroscopic image. For both MRS an MRSI movement changes the magnetic field inhomogeneity, which requires dynamic reshimming. Frequency drifts in MRS and MRSI degrade water suppression, prevent coherent signal averaging over the time course of the scan and interfere with gradient encoding, thus leading to a loss in localization. It is desirable to measure object movement and frequency drift and to correct object motion and frequency drift without interfering with the MRS and MRSI data acquisition.
2. Description of the Prior Art
High-Speed MR Spectroscopic Imaging:
High speed MRSI integrates spatial encoding modules into the spectral acquisition. We have developed Proton-Echo-Planar-Spectroscopic-Imaging (PEPSI) which employs echo-planar readout gradients to accelerate spatial encoding times by more than one order of magnitude as compared to conventional techniques to measure 2-dimensional metabolite distributions at short TE and 3-dimensional metabolite distributions (1,2). PEPSI has also been employed for time-resolved metabolic imaging to dynamically map lactate concentrations during respiratory and metabolic challenges (3,4), to characterize metabolic dysfunction during sodium-lactate infusion in patients with panic disorder (5) and to map multiplet resonance in human brain at short echo time and high field strength (6). We have further increased the encoding speed of high-speed MRSI by combining Proton-Echo-Planar-Spectroscopic-Imaging (PEPSI) with parallel imaging to obtain up to 4-fold acceleration and measurement times of 16 s for a 32×32 matrix with TR 2 s (7) on a 4 Tesla scanner. This technology is particularly advantageous for 3-dimensional spatial mapping and further improvement in encoding efficiency enabled single-shot MRSI (8) in our laboratory.
Motion Detection and Correction
The first on-line prospective real-time methods used straight-line navigators to detect linear motion of organs in the chest (9). These techniques are not applicable in brain scans where rigid body motion in any arbitrary plane and along any axis is possible. In a series of papers, researchers at the Mayo Clinic describe the concepts of orbital and spherical navigators for prospective rigid body motion detection and correction. The orbital (circular) navigator enables the detection of rotation within the plane of the navigator and translations along multiple axes (10, 11). Ward et al. developed a real-time prospective motion correction scheme in which a set of three circular navigators is used to detect motion in all three planes (11). An iterative approach is taken to correct for the motion since the rotations may still be out of the plane of the navigators. The procedure is fairly time consuming and works best for rotations about the cardinal axes. The spherical navigator, first described by Wong and Irarrazabal (12,13) and implemented in a full 3D rigid body measurement application by Welch et al. (14), addresses the problem of off-axis rotations. One implementation of the spherical navigators requires 27 ms for acquisition of the navigator information. Costa et al. have described a 3D rigid body motion correction method using polar spherical navigators (15). By pre-rotating the baseline trajectory of the navigator, the iterations are avoided.
There are no published methods to detect and correct object movement during an ongoing MRS or MRSI scan. Motion correction can be applied post-acquisition using standard registration tools, but the low resolution of the MRSI scan limits the performance of this approach. It is possible to interleave volumetric high resolution MRI scans into the MRS or MRSI scan to detect and prospectively correct movement, but this approach requires additional signal excitation, which interferes with the signal excitation for the spectroscopic acquisition, leading to reduced sensitivity and possible instability in the MRS and MRSI data, and it reduces the temporal resolution of MRS and MRSI.
Compensation of Magnetic Field Inhomogeneity
Magnetic resonance spectroscopic imaging and localized spectroscopy in vivo suffer from microscopic and macroscopic magnetic field inhomogeneity that broaden spectral lines, reduce sensitivity and impair spectral fitting. This is one of the major limitations of MRS and MRSI in vivo. Conventional means of compensating such inhomogeneity include: (a) shimming, which is limited to low shim coils with spatial frequencies and therefore not very effective over large volumes (b) separate acquisition of multiple volumes with different shim settings, which is time consuming (c) increasing spatial resolution, which is very costly in terms of sensitivity and increases measurement time.
Inhomogeneity of the static magnetic field (B0) can be as large as 6 parts-per-million (ppm) across the brain (16,17). These spatial nonlinearities of local gradients are an important limiting factor in volumetric MRSI studies. Higher order auto-shimming (HOAS) provided on most high-field scanners offers limited capability for correction of such imperfections. While all MR processes will benefit from improved shimming to some degree, specific regions of clinical interest, such as the frontal and medial-temporal brain regions, and acquisition techniques, such as MRSI, can be critically affected by shimming effectiveness. In the case of MRS and MRSI, shim state can adversely affect spectral line width, causing artifactual frequency shifts between voxels and decrease effectiveness of water suppression. Furthermore, poorly suppressed water signal can alias into regions of otherwise adequate water suppression as a result of subject motion or k-space undersampling, causing baseline artifact. Aliasing of residual water signals from regions outside of the volume of interest is particularly difficult to identify.
HOAS typically uses a collection of shim coils based on spherical harmonics or other spatial shapes (for a review, see (18)). These coils are powered by current-feedback amplifiers under the control of a user-addressable interface and analysis program. The corrective fields generated by the coils are of finite number, power and extent. Due to time constraints, HOAS attempts to converge to an optimum shim state analytically rather than iteratively, using field maps collected with the existing imaging capability (19-23). Progress in improving existing technique has focused on addressing the limits of the shimming hardware (24-29) and accuracy and stability of the analysis (30,31). However, for MRS and MRSI the performance of HOAS is still insufficient, in particular at high field.
To overcome large local disturbances in field homogeneity, several methods for correction have been proposed. The use of additional passive ferromagnetic shims in a cylindrical array, placed in close proximity to the human head, has been demonstrated (24). Mouthpieces containing diamagnetic shim material (passive shims) have been developed to enhance the Bo homogeneity of the mesioinferior frontal lobes (25,26). Hsu and Glover (27) have taken a similar approach but have used a mouthpiece than contains an active shim coil. However, for clinical applications of spectroscopic imaging these approaches are not practical.
Extending the capability of the existing field coil design requires either more coils of higher order (28), or better control over the existing coils. To increase control, Blamire and colleagues (32) showed that a dynamic shim state, following the current acquisition slice, can improve the corrective power of the shim coils by reducing the spatial constraints on the shim state. Subsequent studies have further demonstrated its effectiveness (33). Dynamic shimming offers greater flexibility in compensating local magnetic field distortion, but applications are currently limited by the considerable hardware demands. However, the clinical manufacturers have identified dynamically switched higher order shims as an important advance and have started product development. It is thus foreseeable that switching higher order shims will become clinical routine.
Frequency Drift Correction
MRS and MRSI are sensitive to frequency drifts during the scan that may arise from scanner instability, field drift, respiration, and shim coil heating due to gradient switching. Frequency drifts degrade water suppression, prevent coherent signal averaging over the time course of the scan and interfere with gradient encoding, thus leading to a loss in localization (34-36). Ebel et al. published a method that collects an additional MRSI data set interleaved into the conventional MRSI data acquisition to detect and correct frequency drifts (36). However, this approach is associated with additional signal excitation, which interferes with the signal excitation for the spectroscopic acquisition, leading to reduced sensitivity and possible instability in the MRSI data, and it reduces the temporal resolution of MRSI. It is desirable to measure this frequency shift and to correct the frequency drift without interfering with the MRSI data acquisition. Ideally, this frequency measurement should be performed in small volumes, since this reduces the effect of magnetic field inhomogeneity and makes the frequency measurement more precise. In addition, it is desirable to simultaneously measure the frequency drift in multiple volumes, since the frequency drift may vary in space [34], e.g. due to breathing or due to gradient drift.
U.S. Pat. No. 6,552,539 discloses a method of correcting resonance frequency variation and MRI apparatus. A method of correcting a resonance frequency variation and an MRI apparatus both capable of handling all frequency drifts including a frequency drift whose time change is slow, a frequency drift in a slice direction and a frequency drift whose time change is fast. An amount of a resonance frequency variation is measured, the frequency variation is corrected when an amount of the resonance frequency variation is smaller than a threshold value, and the amount of the resonance frequency variation is not stored. On the other hand, when the amount of the resonance frequency variation is not smaller than the threshold value, the amount of the resonance frequency variation is stored and correction operation is made based thereon later. This method is not applicable to MRS and MRSI.
U.S. Pat. No. 5,166,620 discloses an NMR frequency locking circuit. An NMR locking mechanism for use with not only electromagnets, superconducting magnets and permanent magnets, but also with ultrahigh energy product magnets such as neodynium. The circuit utilizes a single conversion superheterodyne receiver with a phase locked loop that forms a locking mechanism that depends upon a variable frequency. The resonant frequency of the nuclei is compared to a variable excitation frequency which is adjusted to maintain a control frequency with one unique value of the control frequency being zero at lock. This method is suitable for compensating drifts of the main magnetic field, but it is not suitable to compensate movement or changes in magnetic field inhomogeneity.
High-speed MR spectroscopic imaging has important applications.
The development of hyperpolarized MRI agents presents both unprecedented opportunities and new technical challenges. In particular, with signal-to-noise ratio (SNR) enhancements on the order of the 10000-fold, dynamic nuclear polarization of metabolically active substrates (e.g., 13C-labeled pyruvate or acetate) theoretically permits in vivo imaging of not only the injected agent, but also downstream metabolic products. This feature of hyperpolarized MR spectroscopy (MRS) provides investigators a unique opportunity to non-invasively monitor critical dynamic metabolic processes in vivo under both normal and pathologic conditions. Important applications include tumor diagnosis and treatment monitoring, as well as assessment of cardiac function. In studies using hyperpolarized samples, the magnetization decays toward its thermal equilibrium value and is not recoverable. Therefore, fast spectroscopic imaging acquisition schemes are important.
A recent study by Golman et al. (37) described real-time metabolic imaging. NMR spectroscopy has until now been the only noninvasive method to gain insight into the fate of pyruvate in the body, but the low NMR sensitivity even at high field strength has only allowed information about steady-state conditions. The medically relevant information about the distribution, localization, and metabolic rate of the substance during the first minute after the injection has not been obtainable. Use of a hyperpolarization technique has enabled 10-15% polarization of 13C1 in up to a 0.3 Mpyruvate solution. i.v. injection of the solution into rats and pigs allows imaging of the distribution of pyruvate and mapping of its major metabolites lactate and alanine within a time frame of 10 s. Hyperpolarized MRS is currently being developed by major manufacturers and expected to be of considerable commercial value.
MR spectroscopic imaging in moving organs, like the heart or the breast, is sensitive to movement artifact that results in blurring of the image. Gating to the heart beat is frequently used to reduce motion artifact, but this reduces data acquisition efficiency. Simultaneous synchronization to respiration may be required to further reduce motion artifacts, which additionally reduces data acquisition efficiency. Gating in the presence of irregular heart beat introduces variability in repetition time that results in non steady-state signal intensity and distortion of the image encoding process. Image registration during post-processing is challenging due to the highly nonlinear movement pattern within the chest. High-speed spectroscopic imaging acquisition schemes considerably reduce motion sensitivity.
MR spectroscopic imaging in organs, like the brain, is sensitive to localized signal fluctuations due to blood pulsation or other physiological movement mechanisms (e.g. CSF movement) that results in blurring of the image. Gating to the rhythm of the physiological fluctuation (e.g. heart beat) can be used to reduce this artifact, but this reduces data acquisition efficiency. Gating in the presence of irregular heart beat introduces variability in repetition time that results in non steady-state signal intensity and distortion of the image encoding process. Therefore, fast spectroscopic imaging acquisition schemes are important.
This method is also applicable to spatial mapping chemical reactions for applications in material science and biology. For example, the spatial evolution of a chemical chain reaction could be observed. Such reactions are typically very fast and fast spectroscopic imaging acquisition schemes are thus important to avoid blurring of the spectroscopic images.